Genetic analysis is a promising avenue in psychiatric research. Defining a psychogenetic substrate would greatly enhance validating criteria for illness classification and would contribute to morbid risk prediction. Recent advances in quantitative genetics, diagnostic and biologic concepts of mental illness permit, for the first time, a critical test of genetic hypotheses of schizophrenia. A spectrum of schizophrenia-related states will be defined by matching the morbidity risk for mental disorders among first-degree relatives of schizophrenics with comparable data on normal controls. Illness subforms within the heterogeneous schizophrenia spectrum will be determined by current diagnostic and prognostic concepts. Family data on platelet monoamine oxidase activity, claimed to identify vulnerability to some schizophrenic subsets, will also be gathered. Recently formulated multiple-threshold models of inheritance will be applied to the data, assuming that liability thresholds can be defined by clinical and/or biological subtypes. Modes of inheritance, illness susceptibility and subsumption of disease-forms under a single genetic diathesis will thus be examined. The proposed strategy has not as yet come under investigative scrutiny in schizophrenia research.